1. Field of the Invention
The present invention generally relates to a fluid handing apparatus. More specifically, the invention relates to a fluid handing apparatus for forming a liquid-liquid interface level in a connecting portion in which a flow passage is connected to another flow passage (i.e., in a junction between flow passages), and a fluid handling apparatus for forming a liquid-liquid interface level in each of a plurality of connecting portions, in each of which a flow passage is connected to another flow passage, to meter a very small amount of liquid between the connecting portions and/or to move a charged material in a metered liquid by electrophoresis.
2. Description of the Prior Art
There is known a fluid handling apparatus for efficiently carrying out the crystallization of a protein by the moving boundary diffusion method (or carrier-free diffusion method) via a liquid-liquid interface level formed between a reagent and a solution of the protein by opening a shut-off valve by which a first flow passage containing the reagent is separated from a second flow passage containing the solution of the protein. In such a fluid handling apparatus, a pressure passage for operating a shut-off valve is arranged so as to be close to a flow passage, and a part of the wall of the flow passage is elastically deformed by the pressure of a fluid in the pressure passage for closing the flow passage (see, e.g., U.S. Patent Publication No. 2005/0019794).
However, such a conventional fluid handling apparatus has a complicated structure and is required to have a pressurizing means, since the shut-off valve is formed in a fine flow passage (or microchannel). Therefore, there is a problem in that the whole structure of the apparatus including the pressurizing means is large.
There has been developed a fluid handling apparatus for metering a very small amount of liquid, which contains an analyzing object (a target material) such as a protein or a nucleic acid in an organism, in a flow passage to move the very small amount of liquid due to electrophoresis to detect and analyze the analyzing object in the liquid by means of a measuring device which is arranged in the flow passage.
FIGS. 19A through 19F show a first example of such a conventional fluid handling apparatus. The conventional fluid handling apparatus 100 shown in FIGS. 19A through 19F is made of polydimethylsiloxane (PDMS) which is a material having a high gas permeability, and comprises: a first linear flow passage 101 for moving a liquid sample containing an analyzing object (protein, nucleic acid, DNA or the like) due to electrophoresis; a second flow passage 102 serving as a sample feeding passage which is connected to the middle of the first flow passage so as to be orthogonal thereto; and ports 103, 104 and 105 which are formed in both end portions of the first flow passage 101 and the end portion of the second flow passage 102, respectively. The first flow passage 101 of the fluid handling apparatus 100 has a pair of stop valves 106a and 106b for abruptly decreasing the flow passage area (cross-sectional area) of the first flow passage 101 to dam the stream of a liquid. As shown in FIG. 19A, between the stop valves 106a and 106b, the second flow passage 102 is connected to the first flow passage 101 near the stop valve 106a upstream in electrophoresis directions (on the left side in FIGS. 19A through 19F).
As shown in FIG. 19B, the fluid handling apparatus 100 with this construction is housed in a vacuum equipment 107 to exhaust gas in the fluid handling apparatus 100 (including gas in the first and second flow passages 101 and 102). Then, as shown in FIG. 19C, after the first and second flow passages 101 and 102 are in a vacuum state, a liquid sample 110 containing DNA is dropped into the port 105 which is arranged in the end portion of the second flow passage 102, and polymer solutions 111 and 112 are dropped into the ports 103 and 104 which are arranged in both end portions of the first flow passage 101, respectively. Then, as shown in FIG. 19D, the sample 110 is sucked (fed) by a negative pressure into the first flow passage 101 between the pair of stop valves 106a and 106b via the second flow passage 102. In addition, the polymer solution 111 is sucked (fed) by a negative pressure into the first flow passage 101 between the port 103 and the stop valve 106a, and the polymer solution 112 is sucked by a negative pressure into the first flow passage 101 between the port 104 and the stop valve 106b, so that the first flow passage 101 is filled with the polymer solutions 111, 112 and the sample 110.
If the fluid handling apparatus 100 is designed so that the first flow passage 101 has a desired volume between the pair of stop valves 106a and 106b, it is possible to meter a desired amount of sample 110. Then, electrodes are arranged in the ports 103 and 104, which are arranged in both end portions of the first flow passage 101, and in the port 105 which is arranged in the end portion of the second flow passage 102. Then, a voltage is applied to the liquids (the polymer solutions 111, 112 and the sample 110) in the first flow passage and second flow passage 102 to return the analyzing object, which is arranged in the second flow passage 102, toward the port 105 (see FIGS. 19E and 19F), and to cause the analyzing object, which is contained in the sample 110 in the first flow passage 101, to move in the first flow passage 101 beyond the stop valve 106b (the right stop valve in the figure) to the right (in the direction of D in the figure) due to electrophoresis, so that only a predetermined amount of analyzing object arranged between the stop valves 106a and 106b can be accurately analyzed by means of a measuring device arranged between the stop valve 106b and the port 104 (see, e.g., “SINGLE-STEP CONCENTRATION AND SEQUENCE-SPECIFIC SEPARATION OF DNA BY AFFINITY MICROCHIP ELECTROPHORESIS”, 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Sep. 26-30, 2004).
However, in the above described first example of the conventional fluid handling apparatus 100, it is required to exhaust gas in the flow passages (the first and second flow passages 101, 102) in the vacuum equipment 107, so that there are problems in that the apparatus is large and it takes a lot of time to carry out a pretreatment (a preliminary work before the start of a sample analyzing operation).
FIGS. 20A through 20D show a second example of a conventional fluid handling apparatus. The fluid handling apparatus 200 shown in FIGS. 20A through 20D has flow passages C and D for connecting parallel flow passages A and B to each other. The flow passage area of the flow passage D is abruptly decreased so as to be a far smaller flow passage area than that of the flow passages A, B and C. To the flow passage D, a degassing flow passage E is connected. Among these flow passages A through E, the wall surface of the flow passage D is difficult to be wet (easy to cause repulsion in capillary tube), so that a liquid can not move in the flow passage D due to capillarity. On the other hand, the wall surfaces of the flow passages A and C are easy to be wet (easy to cause capillarity), and the flow passage area of the flow passage C is smaller than that of the flow passage A.
Thus, if a liquid sample 201 is fed into the flow passage A of the fluid handling apparatus 200, the sample 201 in the flow passage A is sucked into the flow passage C due to capillarity. However, the sample 201 entering the flow passage C is dammed (or stopped) by the flow passage D, so that a predetermined amount of sample 201 is metered in the flow passage C (see FIG. 20B). Furthermore, since a polymer solution 202 for moving an analyzing object, which is contained in the sample 201, due to electrophoresis is filled in the flow passage B, the sample 201 in the flow passage A can not be fed into the flow passage C due to capillarity if gas is contained in the flow passage C. Therefore, when the sample 201 in the flow passage A is fed into the flow passage C, the flow passage E is open to exhaust gas in the flow passage C to the outside via the flow passage E.
In such a state, a pressure (gas pressure) at a first stage is applied to the flow passage A to such an extent that the sample 201 in the flow passage C does not escape from the flow passage D toward the flow passage B and that the sample 201 in the flow passage A is moved downstream (to the right in the figure) of the connecting portion of the flow passage A to the flow passage C, so that a predetermined amount of sample 201 is metered in the flow passage C (see FIG. 20C). Thereafter, a pressure (gas pressure) at a second stage, which is a higher pressure than the pressure at the first stage, is applied to the flow passages A and C to such an extent that the sample 201 in the flow passage C passes through the flow passage D to the flow passage B. As a result, the sample 201 in the flow passage C moves into the flow passage B via the flow passage D (see FIG. 20D). Furthermore, when the sample 201 in the flow passage C is moved toward the flow passage B via the flow passage D, the degassing flow passage E is closed.
Then, a voltage is applied to both ends of the flow passage B to move the analyzing object of the sample 201, which is fed into the flow passage B from the flow passage C via the flow passage D, due to electrophoresis (see, e.g., Japanese Patent Laid-Open No. 2004-163104).
However, in the above described second example of the conventional fluid handling apparatus 200, the flow passage E is closed when the sample 201 in the flow passage C is moved to the flow passage B via the flow passage D, so that there is the possibility that gas remaining in the flow passage D is mixed with the sample 201 in the flow passage B to prevent the sample 201 from being smoothly moved by electrophoresis. In addition, since pressures at two stages must be applied to the flow passage A in the fluid handling apparatus 200, operation is complicated. Moreover, since a pressurizing means must be connected to the flow passage A, the structure of the apparatus is complicated, and the whole structure including the pressurizing means and so forth is large.
As a third example of a conventional fluid handling apparatus for use in the analysis of a sample such as a protein or nucleic acid, there has been developed a fluid handling apparatus (a chip for electrophoresis) capable of accurately metering a very small amount of sample, which is required to carry out analysis, to quantitatively analyzing the sample. Such a fluid handling apparatus uses a gas control device for preventing gas from remaining in a flow passage, so that it is possible to form a sample piece, which contacts a buffer solution on a liquid-liquid interface level, in a flow passage for electrophoresis (see, e.g., Japanese Patent Laid-Open No. 2005-114433).
However, in order to exhaust gas from the third example of the conventional fluid handling apparatus, it is required to control positive/negative pressure by the gas control device, so that operation is complicated. In addition, there is a problem in that the structure of the whole apparatus including the gas control device is complicated and large.